Feline heart disease may develop as the result of a variety of different etiologies including nutritional, infectious, endocrine, and inherited, among others. This discussion will focus on what is known about inherited heart disease in cats.

Inherited congenital heart disease in the cat is not common. Endomyocardial fibrosis is characterized by left atrial and ventricular dilation with severe endocardial thickening. It has been shown to be inherited in the Siamese, Burmese breeds, and domestic shorthair cats.

The most common adult-onset disease is cardiomyopathy. There are several different forms of cardiomyopathy in the cat, although hypertrophic is the most common form best shown to be inherited. Causative genetic mutations have now been identified in both the Ragdoll and the Maine Coon. A number of small families of cats with affected members have been reported in additional breeds, including the Norwegian Forest cat, American shorthair, Siberian, Bengal, and Scottish Fold, among others. A useful and frequently updated website for veterinarians and cat breeders interested in future developments in familial feline hypertrophic cardiomyopathy, as well as other feline inherited diseases, is maintained by the Feline Advisory Board www.fabcats.org/breeders/inherited_disorders/index.php.

Hypertrophic cardiomyopathy is the most common form of heart disease in the cat. It is an adult-onset myocardial disease known to be inherited in the Maine Coon and Ragdoll breeds and thought to be inherited in Norwegian Forest, Siberian, Sphynx, and Bengal cats among others. Causative genetic mutations have now been identified in the Maine Coon and Ragdoll.

Hypertrophic cardiomyopathy is inherited as an autosomal dominant trait in the Maine Coon. Autosomal dominant traits should have the following criteria: males and females are generally equally affected; every affected individual should have at least one affected parent; and the trait is generally observed in every generation.

In the Maine Coon, a genetic mutation has been identified in the myosin-binding protein C (MYBPC3) gene. Myosin-binding protein C is the second most commonly mutated gene responsible for the human form of the disease. In the Maine Coon cat, the mutation is a single base pair change from a guanine to a cytosine in the 31st codon of the gene. This mutation changes the structure of myosin-binding protein C and alters the ability to interact with other contractile proteins. The Maine Coon mutation appears to be quite breed specific. It is unlikely to be associated with hypertrophic cardiomyopathy in other breeds of cats unless they are closely related to the Maine Coon breed.

A substitution mutation has also been identified in the myosin-binding protein C gene in the Ragdoll cat. However, the Ragdoll mutation is different from the Maine Coon mutation and is a cytosine to thymine substitution in the 820th codon. It is extremely unlikely that the Maine Coon and Ragdoll mutations were inherited from a common ancestor since the mutations are different and are located in such different regions of the gene. Although the mode of inheritance of this mutation in the Ragdoll has not been identified through breeding studies, it is most likely an autosomal dominant trait as well. In the Ragdoll, homozygous cats appear to be very severely affected with development of heart failure and thromboembolic episodes often before 2 years of age. Heterozygous cats appear to have a much more mild form of the disease that may include only mild papillary muscle hypertrophy. The Ragdoll mutation also appears to be breed specific to the Ragdoll.

Genetic testing is now available to test a cat for either mutation by submitting a DNA sample to a reputable screening laboratory. Good-quality DNA samples can be obtained either from a blood sample in an EDTA tube or by brushing the oral gums of the cat with a special buccal swab, although many labs will even accept samples submitted on a cotton swab.

The test results should verify that the cat is negative, heterozygous, or homozygous for the mutation. Cats that test negative do not have the mutation. This does not mean that they cannot ever develop hypertrophic cardiomyopathy; it simply means that they will not develop the form of the disease caused by the specific genetic mutation. Although these mutations have been shown to be the cause of hypertrophic cardiomyopathy in many Maine Coons and Ragdoll cats, there are some cats that are echo positive for hypertrophic cardiomyopathy that do not have the specific mutations.

Due to an apparently fairly high prevalence of the mutation in both breeds, it would seem to be unwise to recommend that all cats with the mutation be removed from the breeding programs since this could result in dramatically altering the genetic makeup of these breeds. Additionally, it should be emphasized that not all cats that have the mutation, particularly if they are heterozygous, will develop a clinical form of the disease. Our current recommendations for both breeds are to not use cats that are homozygous for the mutation for breeding purposes since they will certainly pass on the mutation and they have the highest risk of developing the disease. Heterozygous cats should be carefully evaluated. Cats that have many strong positive breed attributes and are disease negative at time of breeding could be bred to a mutation-negative cat. Their lack of clinical disease may suggest that they have a less penetrant form of the disease or that they just do not show evidence of this adult-onset clinical disease yet. Therefore, these cats should only be used if they are exceptional for the breed, and they should be clinically evaluated for the disease every year. If they develop the clinical disease, they should no longer be kept in the breeding program. The offspring of the mating of a positive heterozygous and a negative should be screened for the mutation, and if possible, a mutation-negative kitten with desirable traits should be selected to replace the mutation-positive parent in the breeding colony. Over a few generations, this will decrease the prevalence of the disease mutation in the population, hopefully without greatly altering the genetic makeup of the breed too significantly. Finally, disease-negative but mutation-positive cats should be evaluated annually for presence of disease.